{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:25:14Z","timestamp":1789647914651,"version":"4.0.0"},"reference-count":85,"publisher":"The Company of Biologists","issue":"6","license":[{"start":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T00:00:00Z","timestamp":1654819200000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["R01NS102261"],"award-info":[{"award-number":["R01NS102261"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"crossref","award":["R01DE026737"],"award-info":[{"award-number":["R01DE026737"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100011781","name":"Shriners Hospitals for Children","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011781","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100007707","name":"University of California, Davis","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007707","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Neural tube defects (NTDs) are among the common and severe birth defects with poorly understood etiology. Mutations in the Wnt co-receptor LRP6 are associated with NTDs in humans. Either gain-of-function (GOF) or loss-of-function (LOF) mutations of Lrp6 can cause NTDs in mice. NTDs in Lrp6-GOF mutants may be attributed to altered \u03b2-catenin-independent noncanonical Wnt signaling. However, the mechanisms underlying NTDs in Lrp6-LOF mutants and the role of Lrp6-mediated canonical Wnt\/\u03b2-catenin signaling in neural tube closure remain unresolved. We previously demonstrated that \u03b2-catenin signaling is required for posterior neuropore (PNP) closure. In the current study, conditional ablation of Lrp6 in dorsal PNP caused spinal NTDs with diminished activities of Wnt\/\u03b2-catenin signaling and its downstream target gene Pax3, which is required for PNP closure. \u03b2-catenin-GOF rescued NTDs in Lrp6-LOF mutants. Moreover, maternal supplementation of a Wnt\/\u03b2-catenin signaling agonist reduced the frequency and severity of spinal NTDs in Lrp6-LOF mutants by restoring Pax3 expression. Together, these results demonstrate the essential role of Lrp6-mediated Wnt\/\u03b2-catenin signaling in PNP closure, which could also provide a therapeutic target for NTD intervention through manipulation of canonical Wnt\/\u03b2-catenin signaling activities.<\/jats:p>","DOI":"10.1242\/dmm.049517","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T07:52:17Z","timestamp":1651823537000},"source":"Crossref","is-referenced-by-count":13,"title":["The role of Lrp6-mediated Wnt\/\u03b2-catenin signaling in the development and intervention of spinal neural tube defects in mice"],"prefix":"10.1242","volume":"15","author":[{"given":"Tianyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"},{"name":"University of California, Davis School of Medicine , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1871-0804","authenticated-orcid":false,"given":"Moira","family":"McMahon","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"},{"name":"University of California, Davis School of Medicine , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"},{"name":"University of California, Davis School of Medicine , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1325-3499","authenticated-orcid":false,"given":"Subbroto Kumar","family":"Saha","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"},{"name":"University of California, Davis School of Medicine , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Stokes","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"},{"name":"University of California, Davis School of Medicine , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8592-4680","authenticated-orcid":false,"given":"Chengji J.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute for Pediatric Regenerative Medicine of Shriners Hospitals for Children-Northern California , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"},{"name":"University of California, Davis School of Medicine , Department of Biochemistry and Molecular Medicine , , Sacramento, CA 95817 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"2022061007571148000_DMM049517C1","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1093\/hmg\/ddt558","article-title":"Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway","volume":"23","author":"Allache","year":"2014","journal-title":"Hum. 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